Esketamine Shows Potential in Reducing Postpartum Depression After Cesarean Delivery: JAMA

PPD is a significant mental health concern affecting many new mothers, particularly after cesarean deliveries, which are often associated with higher stress levels and longer recovery periods. While standard treatments for PPD include psychological support and antidepressants, there is growing interest in preventive strategies to reduce the risk of developing the condition as it affects approximately 18% of postpartum women worldwide, significantly influencing parent-child bonding.

Randomized clinical trials have shown that esketamine can lower the incidence of postpartum depression. However, its effectiveness in real-world clinical settings remains uncertain. Considering this, Li Ren, Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, and colleagues aimed to evaluate the effectiveness of administering esketamine during surgery in preventing postpartum depression among women undergoing cesarean delivery.

For this purpose, the researchers conducted a randomized clinical trial at The First Affiliated Hospital of Chongqing Medical University from March 2023 to February 2024. Pregnant women scheduled for cesarean delivery were included, except those with intellectual dysfunction or contraindications to esketamine. Participants were randomly assigned to receive either 0.25 mg/kg esketamine in saline or a saline placebo over 20 minutes.

The primary outcome was the incidence of postpartum depression at six weeks, assessed using the Edinburgh Postnatal Depression Scale. Data analysis followed the intention-to-treat principle to evaluate esketamine’s potential in reducing PPD risk.

The study led to the following findings:

• A total of 308 pregnant women were randomly assigned to two groups: esketamine (154 participants, mean age 31.57 years) and control (154 participants, mean age 32.53 years).
• The incidence of postpartum depression at six weeks was lower in the esketamine group (10.4%) compared to the control group (19.5%).
• The relative risk of developing PPD in the esketamine group was 0.53.
• The difference between the two groups was statistically significant.

The researchers found that intraoperative esketamine infusion reduced the incidence of postpartum depression (PPD) at six weeks among patients undergoing cesarean delivery. However, there was no significant benefit in one week. They also noted a potential adjunctive analgesic effect, as esketamine reduced the frequency of PCIA bolus administration without significantly impacting pain scores. While more adverse events occurred in the esketamine group immediately after surgery, these effects were generally mild and resolved quickly.

"The study highlights esketamine’s potential for PPD prevention, but further research is needed to confirm its efficacy and safety in clinical practice," the researchers concluded.

Reference:

Ren L, Zhang T, Zou B, et al. Intraoperative Esketamine and Postpartum Depression Among Women With Cesarean Delivery: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(2):e2459331. doi:10.1001/jamanetworkopen.2024.59331